During development, especially in the first few years of life, children show interesting patterns of neural development with a high degree of neuroplasticity. The relation of brain growth and development and cognitive development is poorly understood and an area of growing research.
Some new development intends to prove a link between brain growth and cognitive development in infants and particularly in preterm infants or extremely low gestational age newborns (J. Pediatr. 2009; 155:344-9).
Thus, there is a great interest and need in supporting brain growth, particularly in preterm infants, to favor their cognitive and/or psychomotor development.
In particular, there is a need for a nutritional composition for use in brain growth and/or cognitive and/or psychomotor development, in particular in infants and young children, preferably infants, who were born preterm or with low-birth weight (LBW) or experienced intrauterine growth retardation (IUGR) or who suffered from growth stunting because of malnutrition, such as suboptimal intra-uterine nutrition, and/or disease.
Breast milk is the most nutritionally sound food for babies. It consists of nutrients, such as proteins, lipids, carbohydrates, minerals, vitamins, and trace elements that babies need to grow healthy. It also contains immune-related components such as IgA, leukocytes, oligosaccharides, lysozyme, lactoferrin, interferon-γ, nucleotides, cytokines, and others. Several of these compounds offer passive protection in the gastrointestinal tract and to some extent in the upper respiratory tract, preventing adherence of pathogens to the mucosa and thereby protecting the breast-fed infant against invasive infections. Human milk also contains essential fatty acids, enzymes, hormones, growth factors, polyamines, and other biologically active compounds, which may play an important role in the health benefits associated with breast-feeding.
Human milk is particularly rich in lactose based oligosaccharides. These generally non-digestible oligosaccharides are extensions of the milk sugar lactose brought about by the action of a series of glycosyltransferases such as those transferring N-acetyl-glucosamine, galactose, sialic acid or fucose. Relatively little is known on exactly which glycosyltransferase is involved in the formation of which specific milk oligosaccharide,with the exception of the two fucosyltransferases FUT2 (secretor gene) and FUT3 (Lewis gene). Both are known to be involved in the formation of the different fucosyl-oligosaccharides, because both are polymorphic with different alleles leading to null mutations and missing enzyme activity. The consequent varying enzyme activities manifest in measurable variation of specific fucosyl-oligosaccharides.
Cognitive and psychomotor development has been proposed to be promoted by supplementation with long-chain poly-unsaturated fatty acids and a number clinical trials have investigated this hypothesis. However, a recent meta-analysis that combined these data showed no significant effect of supplementation on neurodevelopment (Schulzke S M, Patole S K, Simmer K, Longchain polyunsaturated fatty acid supplementation in preterm infants (Review) The Cochrane Library 2011, Issue 2).
Cognitive development can be also improved in preterm infants by largely increasing the protein and energy intake (I Brandt, E. J. Sticker and M. J. Lentze, catch-up growth of head circumference of very low birth weight, small for gestational age preterm infants and mental development to adulthood, J. Pediatr. 2003; 142:463-8). However, large enteral feeding volumes and/or high protein/energy density of the feeds can induce intolerance to feeding. In addition, high protein intake, which leads to increased urea production, may increase the risk of renal insufficiency and metabolic acidosis in preterm infants. Furthermore, high protein/energy intake during infancy has been associated to long-term alterations on metabolic health (increased risk of obesity, type II diabetes and cardiovascular disease) (KK ONG & RJF LOOS, Rapid infancy weight gain and subsequent obesity: Systematic reviews and hopeful suggestions; Acta Paediatrica, 2006; 95: 904-908; J Rotteveel, M M van Weissenbruch, J W R Twisk, H A Delemarre-Van de Waal, Infant and Childhood Growth Patterns, Insulin Sensitivity, and Blood Pressure in Prematurely Born Young Adults Pediatrics 2008; 122: 313-321).
WO 2014/043368 and WO 2013/057049 propose methods and compositions for improving brain growth and cognitive development and for enhancing memory functions in individuals by administering human milk oligosaccharides. However, io these methods and compositions are not specifically suited for use infants or preterm infants in the very early postnatal period.
Thus, there is still a need for improved nutritional compositions for use in promoting brain growth and development in infants, and, in particular, in pre-term infants with low-birth weight (LBW) and infants who experienced intrauterine growth retardation (IUGR) or who suffered from growth stunting because of malnutrition, such as suboptimal intra-uterine nutrition, and/or disease.
Further, there is a particular need for nutritional compositions for use in infants born from mothers who are naturally expressing low levels of Fucosyltransferase 2 (Fut2). It was surprisingly found by the present inventors that the breast milk of these Fut2-deficient mothers is not only poor in Fucosyltransferase 2 (Fut2)-dependent oligosaccharides, but also comprises lower levels of other human milk oligosaccharides such as Lacto-N-Neotetraose (LNnT), as compared to the LNnT levels found in the breast milk from mothers expressing high levels of Fut2.
Thus, there is also a particular need to supplement the nutrition of infants during the lactation period in order to insure optimum levels of Fucosyltransferase 2 (Fut2)-dependent oligosaccharides and Lacto-N-Neotetraose (LNnT) during said period.
Moreover, there is a particular need for bridging the nutritional gap regarding Fucosyltransferase 2 (Fut2)-dependent oligosaccharides and Lacto-N-Neotetraose (LNnT) that may appear during the weaning period and after the stop of breast feeding. These needs are met by the subject-matter of the present invention as disclosed below.